Continuous efforts are being made to develop new and improved biocompatible materials for the manufacture of medical devices, medical articles or materials used for various medical treatments. Generally, biocompatibility is achieved by designing materials that resist the adsorption and deposition of proteins, cells, and/or bacteria. The applications for such biocompatible materials are numerous, and include materials for prostheses, tissue substitutes, wound dressings, materials for the transfer of drugs and vaccines, and sensing devices. These materials can also be useful to prevent fouling, such as in watercraft devices that tend to accumulate bacteria, mold or marine organisms.
Surfaces including a low density distribution of high molecular weight ethylene glycol units have been reported to be effective for resisting the adsorption of proteins. Du et al. describes grafting poly(ethylene glycol) on lipid surfaces to inhibit the adsorption of proteins and cells (Biochimica et Biophysica Acta, Vol. 1326, pp. 236-248, 1997). Substrate surfaces have also been derivatized with poly(ethylene glycol) units via self-assembled monolayers. Harder et al. describes silver and gold surfaces bonded to n-alkanethiolates derivatized with oligo(ethylene glycol)-terminated units (J. Phys. Chem. B, Vol. 102, pp. 426-436, 1998). Prime et al. describes mixed self-assembled monolayers on gold in which oligo(ethylene oxide)-grafted alkanethiolate chains are mixed with alkanethiolate chains (J. Am. Chem. Soc., Vol. 115, pp. 10714-10721, 1993).
Cunliffe et al. describes silica surfaces derivatized with poly(ethylene oxide) that exhibit resistance to the adsorption of bacteria (Applied and Environmental Microbiology, Vol. 65 (11), pp. 4995-5002, November 1999).
Oligo(ethylene glycol) units are disadvantageous, however, because these units can be susceptible to autoxidation. Thus, there is a need for surfaces derivatized with compositions other than ethylene glycol units. Van der Heiden describes a poly(ether urethane) surface derivatized with phosphorylcholine to produce a passivated surface towards protein adsorption and platelet adhesion (J. Biomed. Mater. Res. Vol. 40, pp. 195-203, 1998). Deng et al. describes a surface containing self-assembled monolayers of tri(propylene sulfoxide) groups, which can be mixed with alkane terminated chains, to prepare surfaces which resist the adsorption of proteins (J. Am. Chem. Soc., Vol. 118, pp. 5136-5137, 1996).
Certain polymers also display protein-resistant properties. U.S. Pat. No. 4,241,682 (Konstandt) describes the use of a polymeric solution which can be coated onto a painted surface to increase the life of the painted surface. The solution includes a mixture of polyethylenimine and a hydrophilic acrylic polymer. U.S. Pat. No. 5,312,873 describes polymers having surface nitrile groups which are converted to amides, resulting in a membrane that resists absorptive fouling. U.S. Pat. No. 4,925,698 (Klausner et al.) describes a chemical modification of polymeric surfaces that renders the polymers more resistant to the deposition of proteins. In particular, the chemical modification involves acylation.
As there is no material that completely resists the adsorption of proteins, cells and bacteria, there remains a need to develop new materials.